Clinically Significant Genes in CNS Working Group
Working Group Charter
Clinically Significant Genes in CNS Tumors: An Evidence-Based Consensus Review from the Cancer Genomics Consortium Working Group
Work Product Category
Manuscript or Publication: Statement of Clinical Utility/Review of genetic/genomic abnormalities and their clinical significance
Specific Aims for the Work Product
A previous effort by the Cancer Genomics Consortium (CGC) working group on primary CNS tumors (PMID: 32203924) reviewed relevant clinical studies and summarized copy number alterations (CNAs) of clinical significance in primary CNS tumors. The goal of this working group is to review and summarize the list of genes of clinical significance.
To compile a comprehensive list of genes altered in primary CNS tumors using TCGA and major guidelines (WHO, NCCN, EANO, cIMPACT-NOW) and the gene panels used at WG members’ primary institutions.
To conduct rigorous literature review to evaluate diagnostic, prognostic and therapeutic clinical significance of every gene mainly following the CGC SOP (myeloid/lymphoid WG in progress) with some modification as needed.
To create the master table of genes of proven significance.
To analyze the data and to create additional figures as needed (pathway enrichment analysis, OncoPlot, Venn diagrams, distribution of genes on chromosomes, etc.).
To create .bed files.
Post-manuscript publication, the group will work on CNS in CCGA.io
The molecular characterization of Central Nervous System (CNS) tumors has resulted in an exponential growth in the genomic, transcriptomic and epigenetic events that impact diagnosis, prognosis, and treatment. The current diagnostic evaluation requires not only morphologic examination of the tumor tissue, but also a multimodal set of molecular tests which have been adopted into clinical diagnostic practice. In response to this paradigm shift, the Cancer Genomics Consortium (CGC) assembled an expert “CNS Tumor Gene list” working group with the goal of developing a CNS tumor gene list, a comprehensive resource for clinical laboratory testing engaged in the care of neuro-oncology patients. In developing the gene list, our aims were to categorize all relevant genes as to their diagnostic, prognostic and therapeutic significance, using an evidence-based tiering system. Following a previously developed evidence-based framework for assessment of significance of genes in specific tumor types, we conducted a structured literature search, followed by systematized consensus review. Here we present a curated list of 463 genes identified through this process, with associated molecular pathways. Common genetic drivers between different CNS tumor entities are synthesized, such as inactivating mutations or deletions affecting tumor suppressor genes or gain-of-function mutations, amplifications, or activating fusions involving proto-oncogenes. Novel genetic alterations have also been captured through our wide-ranging literature search. The CGC CNS tumor gene list therefore provides a supportive resource for clinical testing, offers rational design of molecular diagnostic panels, and informs translational research in neuro oncology.
Working Group Members
Madina Sukhanova
Northwestern University Feinberg School of Medicine
Laveniya Satgunaseelan
Royal Prince Alfred Hospital
Malak Abedalthagafi
Tufts Medical Center and Tufts School of Medicine
Xiaolin Hu
Clinical Genetics, GeneDx
Cristiane Ida
Mayo Clinic
Pouya Jamshidi
Northwestern University Feinberg School of Medicine
Stewart Neill
Emory University School of Medicine
Lucas Santana-Santos
Northwestern University Feinberg School of Medicine
Angela Lager
University of Chicago